Open Access

Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer

  • Authors:
    • Jiayu Mao
    • Xueqi Chen
    • Chunsaier Wang
    • Wenbin Li
    • Jingnan Li
  • View Affiliations

  • Published online on: April 16, 2020     https://doi.org/10.3892/ol.2020.11545
  • Pages: 337-345
  • Copyright: © Mao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The downregulation of farnesoid X receptor (FXR; gene name, nuclear receptor subfamily 1 group h member 4), an enteric nuclear bile acid receptor, has been reported in colorectal carcinoma (CRC), and FXR expression has been inversely correlated with CRC stage and clinical outcome. FXR knockdown in chronic colitis mouse models of intestinal tumorigenesis results in early mortality and increased tumor progression via promoting Wnt signaling. The aim of the present study was to explore the effects and mechanism of FXR on the Wnt/β‑catenin signal pathway in CRC. FXR and β‑catenin protein expression levels were detected in an ulcerative colitis mouse model and human colon cancer cell lines (HT‑29, Caco‑2 and HCT‑116). Gain‑ and loss‑of‑function studies were conducted by transfecting colon cancer cells with FXR siRNA and treating them with the FXR agonist GW4064. Subsequently, β‑catenin transcriptional activity was measured using the dual‑luciferase assay, and β‑catenin/TCF4 complex levels and β‑catenin protein and mRNA expression levels were determined. FXR and β‑catenin expression levels were inversely associated in both the animal model and colon cancer cells. The Wnt signaling pathway was activated by increased β‑catenin/TCF4 complex levels upon FXR silencing; however, mRNA and protein levels of β‑catenin were not significantly affected. The FXR agonist GW4064 significantly inhibited the proliferation of cells but promoted the transcriptional activity of β‑catenin. Thus, the present study demonstrated that FXR influences the Wnt/β‑catenin signaling pathway. Furthermore, loss of FXR expression promotes the transcriptional activity of β‑catenin, whereas FXR activation results in the opposite effect.

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July 2020
Volume 20 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Mao, J., Chen, X., Wang, C., Li, W., & Li, J. (2020). Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer. Oncology Letters, 20, 337-345. https://doi.org/10.3892/ol.2020.11545
MLA
Mao, J., Chen, X., Wang, C., Li, W., Li, J."Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer". Oncology Letters 20.1 (2020): 337-345.
Chicago
Mao, J., Chen, X., Wang, C., Li, W., Li, J."Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/β‑catenin signaling pathway in colon cancer". Oncology Letters 20, no. 1 (2020): 337-345. https://doi.org/10.3892/ol.2020.11545